Quantification of the familial contribution to juvenile idiopathic arthritis

Abstract

Objective. We previously demonstrated that there is familial aggregation of juvenile idiopathic arthritis (JIA). Using a large JIA cohort, we sought to identify additional clusters of JIA cases and to calculate robust estimates of the relative risk (RR) of JIA in the siblings and cousins of JIA probands. We also estimated the population attributable risk (PAR) of familial factors in JIA.Methods. A probabilistic record-linking analysis was performed by matching the records of 862 patients with JIA with the records of ϳ7 million individuals in the Utah Population Database (UPDB), a computerized genealogic database. For each patient, 5 control subjects matched for birth year and sex were selected from the UPDB. Specialized software was used to test for familial aggregation of disease, to estimate the magnitude of familial risks, and to identify families at high risk of disease.Results. We identified 22 founders who had significantly more descendants with JIA than expected (5-13 descendants; P values ranged from <0.0001 to <0.008). The PAR of familial factors for JIA was ϳ13%. The RR of JIA in the siblings of patients was significantly increased (11.6, 95% confidence interval [95% CI] 4.9-27.5, P < 2.59 ؋ 10 ؊8 ). The RR of JIA in first cousins was also increased (5.82, 95% CI 2.5-13.8, P < 6.07 ؋ 10 ؊5 ).Conclusion. We have identified the largest sets of JIA pedigrees described to date. Approximately 13% of cases of JIA can be attributed to familial factors. Siblings and first cousins of probands with JIA have an increased risk of JIA. The observed decline in the magnitude of risk between siblings and cousins suggests that JIA is influenced by shared genetic factors.

Is gastroschisis truly a sporadic defect? Familial cases of gastroschisis in Utah, 1997 to 2008

“…This resource has allowed researchers to identify genes for cancer, asthma, and birth defects (Cannon-Albright et al, 1988;Goldgar et al, 1994;Bleyl et al, 2006;Teerlink et al, 2009;Shirts et al, 2010). In addition, the UPDB provides the initial step to evaluate whether there is an increased risk among families for many conditions and has recently been successful in the identification of a familial risk for juvenile rheumatoid arthritis and developmental dysplasia of the hip (Stevenson et al, 2009b;Prahalad et al, 2010). The UPDB was created in the mid 1970s from genealogy records and included records from the Utah Cancer Registry and Utah death certificates.…”

Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case–Control Study

“…1 Despite the presence of known genetic risk factors, population-based studies suggest that genetics explains only 10% to 25% of disease incidence. 2,3 Environmental triggers such as viral infections have been suggested, [4][5][6] but other studies have not substantiated these findings. [7][8][9][10] One study found that hospitalization for infection in the first year of life was associated with an increased risk of developing JIA.…”

The Etiology of Juvenile Idiopathic Arthritis

“…JIA pathogenesis is still poorly understood: the interaction between environmental factors and multiple genes has been proposed as the most relevant working mechanism to the development of JIA. The frequency of each subtype seems to vary significantly in different countries, and ethnic differences may also depend on both genetic and environmental heterogeneity [7][8][9][10].…”